Christin Müller

Christin Müller
Justus-Liebig-Universität Gießen | JLU · Institute of Medical Virology

Dr. rer. nat.

About

35
Publications
59,217
Reads
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832
Citations
Citations since 2017
30 Research Items
817 Citations
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2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Introduction
Current research activities focus on the biology and pathogenesis of respiratory viruses (incl. corona- and influenza viruses). The main goal of our studies is to obtain a comprehensive understanding of (host) factors and molecular mechanisms involved in viral replication. Information derived from these studies is used to develop new prophylactic and therapeutic strategies to combat respiratory and/or systemic infections caused by these viruses.
Additional affiliations
May 2018 - present
Justus-Liebig-Universität Gießen
Position
  • PostDoc Position
March 2014 - May 2018
Justus-Liebig-Universität Gießen
Position
  • PhD Student

Publications

Publications (35)
Article
Full-text available
Coronavirus replication is associated with intracellular membrane rearrangements in infected cells, resulting in the formation of double-membrane vesicles (DMVs) and other membranous structures that are referred to as replicative organelles (ROs). The latter provide a structural scaffold for viral replication/transcription complexes (RTCs) and help...
Article
Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5' cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay...
Article
Full-text available
Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. The ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in differe...
Article
Full-text available
Circular RNAs (circRNAs) are noncoding RNAs that exist in all eukaryotes investigated and are derived from back-splicing of certain pre-mRNA exons. Here, we report the application of artificial circRNAs designed to act as antisense-RNAs. We systematically tested a series of antisense-circRNAs targeted to the SARS-CoV-2 genome RNA, in particular its...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, a severe respiratory disease with varying clinical presentations and outcomes, and responsible for a major pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, the quest for novel therapeutic solutions remai...
Article
Full-text available
Influenza A virus (FLUAV) is a significant human pathogen. In silico structural analysis (PMID 28628827) has suggested that the FDA-approved drug paliperidone interferes with the binding of the FLUAV polymerase subunit PB2 to the nucleoprotein NP. We found that paliperidone inhibits FLUAV A/PR/8/34 early after infection of canine MDCK II, human A54...
Article
Full-text available
Avian influenza virus (AIV) H9N2 was declared to be endemic in birds of the Middle East, in particular in Egypt, with multiple cases of human infections. Despite concerns about the pandemic threat posed by H9N2 AIV, due to the fact that its receptor specificity is similar to that of human influenza viruses, its morbidity and mortality rates in huma...
Article
Full-text available
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immu...
Article
Full-text available
Rocaglates are potent broad-spectrum antiviral compounds with a promising safety profile. They inhibit viral protein synthesis for different RNA viruses by clamping the 5′-UTRs of mRNAs onto the surface of the RNA helicase eIF4A. Apart from the natural rocaglate silvestrol, synthetic rocaglates like zotatifin or CR-1-31-B have been developed. Here,...
Article
Full-text available
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the...
Preprint
Full-text available
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the...
Article
Full-text available
The Front Cover presents an experimental weapon changing the outcome of a battle in the respiratory system. The picture shows severe acute respiratory syndrome corona virus (SARS‐CoV) particles and the virus′ own papain‐like protease (PLpro, PDB‐ID 3E9S) through the window of a cockpit. The essential protease is targeted and “bombarded” with the no...
Preprint
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus in the subgenus Sarbecovirus causes a respiratory disease with varying symptoms referred to as coronavirus disease 2019 (COVID-19) and is responsible for a pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, and infection a...
Article
Full-text available
The unprecedented spread of H5N8- and H9N2-subtype avian influenza virus (AIV) in birds across Asia, Europe, Africa, and North America poses a serious public health threat with a permanent risk of reassortment and the possible emergence of novel virus variants with high virulence in mammals. To gain information on this risk, we studied the potentia...
Article
Full-text available
Egypt is a hotspot for H5- and H9-subtype avian influenza A virus (AIV) infections and co-infections in poultry by both subtypes have been frequently reported. However, natural genetic reassortment of these subtypes has not been reported yet. Here, we evaluated the genetic compatibility and replication efficiency of reassortants between recent isol...
Article
Full-text available
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the non-covalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl)benzamide (2b), which...
Preprint
Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replicat...
Article
Full-text available
Antiviral therapies against influenza are required, especially for high-risk patients, severe influenza and in case of highly pathogenic influenza virus (IV) strains. However, currently, licensed drugs that target the virus directly are not very effective and often lead to the development of resistant IV variants. This may be overcome by targeting...
Article
Full-text available
Interferons are potent and broadly acting cytokines that stimulate cellular responses to nucleic acids of unusual structures or locations. While protective when induced following viral infections, the induction of interferons is detrimental to the host during L. monocytogenes infection. Here, we identify specific sRNAs, secreted by the bacterium, w...
Article
Full-text available
Infection with IAVs leads to the induction of complex signaling cascades, which apparently serve two opposing functions. On the one hand, the virus highjacks cellular signaling cascades in order to support its propagation; on the other hand, the host cell triggers antiviral signaling networks. Here we focused on IAV-triggered phosphorylation events...
Article
The synthesis of a number of spirocyclic ribonucleosides containing either a triazolic or azetidinic system is described, along with two analogous phosphonate derivatives of the former. These systems were constructed from the same beta-D-psicofuranose starting material. The triazole spirocyclic nucleosides were constructed using the 1-azido-1-hydro...
Article
The common cold is a respiratory disease often caused by viral pathogens, including a major group of human rhinoviruses (HRV). Currently, there is no specific antiviral approach available against these viruses. Another viral pathogen that causes respiratory diseases is the influenza virus (IV). Even though a few approved drugs are available for ant...
Article
Full-text available
Recently, a novel antiviral compound (K22) that inhibits replication of a broad range of animal and human coronaviruses was reported to interfere with viral RNA synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al., 2014). Here we assessed potential antiviral activities of K22 against a range of viruses representing two (sub...
Article
Full-text available
Background Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase f...
Article
Full-text available
RNA viruses cause most of the dangerous communicable diseases. Due to their high mutation rates, RNA viruses quickly evade selective pressures and can adapt to a new host. Therefore, new antiviral approaches are urgently needed, which target more than one specific virus variant and which would optimally prevent development of viral resistance. Amon...
Article
Full-text available
Bacillus pumilus ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectiv...
Article
Full-text available
Influenza viruses (IV) continue to pose an imminent threat to human welfare. Yearly re-occurring seasonal epidemic outbreaks and pandemics with high mortality can occur. Besides vaccination against a limited number of viral strains only a few antiviral drugs are available, which are losing their effectiveness as more and more IV strains become resi...
Article
Full-text available
Coronaviruses (CoV) belong to the large family Coronaviridae within the order of Nidovirales. Among them, several human pathogenic strains (HCoV) are known to mainly cause respiratory diseases. While most strains contribute to common cold-like illnesses others lead to severe infections. Most prominent representatives are SARS-CoV and MERS-CoV, whic...
Article
Full-text available
Safe and efficacious therapeutic options for infections caused by highly pathogenic influenza viruses (IV) remain limited. Viruses resistant to approved antiviral drugs are increasingly emerging and, in some cases, existing vaccines are insufficient to prevent seasonal epidemics or pandemics caused by these viruses. As a consequence, alternative an...
Article
Phosphatidylinositol 4-kinase IIIβ (PI4KB) is indispensable for the replication of various positive-sense single stranded RNA viruses, which hijack this cellular enzyme to remodel intracellular membranes of infected cells to set up the functional replication machinery. Therefore, the inhibition of this PI4K isoform leads to the arrest of viral repl...
Article
The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation initiation complex in eukaryotes, is an important novel drug target in cancer research because its helicase activity is required to unwind extended and highly structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound isolated from the plant Aglaia f...
Article
Full-text available
Unlabelled: Influenza A viruses (IAV) replicate their segmented RNA genome in the nucleus of infected cells and utilize caspase-dependent nucleocytoplasmic export mechanisms to transport newly formed ribonucleoprotein complexes (RNPs) to the site of infectious virion release at the plasma membrane. In this study, we obtained evidence that apoptoti...

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